Administration of 2-butoxyethanol (BE) or 2-methoxyethanol to rats by gavage induced dose-dependent acute hemolytic anemia and testicular toxicity, respectively. Early reports from this laboratory indicated that calcium channel blockers protect against the testicular toxicity of 2- methoxyethanol. In the present work, the effect of calcium channel blockers, verapamil (40 mg/kg; ip) or diltiazem (90 mg/kg; ip) prior to BE resulted in a significant decrease in erythrocytic swelling, ATP depletion, and ameliorated the subsequent BE-induced hemolytic anemia. In vitro, addition of verapamil or diltiazem, at concentrations ranging from 0.25 to 2.0 mM, to blood prior to incubation with BAA, resulted in a time- and concentration-dependent attenuation of swelling, ATP depletion, and hemolysis of erythrocytes. Incubation of erythrocytes with BAA in calcium- free media or addition of EGTA had no effect on BAA activity.